Relative safety and efficacy of topical and oral NSAIDs in the treatment of osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: Osteoarthritis (OA) often affects the hands, knees, and hip joints, causing considerable pain and disability, and often affecting the patient's quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are common pain relievers often applied as first line therapies for OA. However, prolonged NSAIDs application can have unwanted side effects. Given this, this study was designed to systematically evaluate the efficacy and safety of topical and oral NSAIDs for the treatment of OA. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant papers from their inception dates to May 2021. Our study only included randomized controlled trials comparing topical and oral NSAIDs and all data were analyzed using Review Manager version 5.3 (RevMan version 5.3). RESULTS: We identified 8 RCTs (2096 patients with OA), for evaluation and revealed that, in general, topical and oral NSAIDs presented with similar efficacies for the treatment of OA. The Western Ontario and McMaster Osteoarthritis Index for assessing pain relief in OA patients was (standardized mean difference [SMD] 0.07; 95%CI -0.02, 0.17) and visual analog scale was (SMD -0.01; 95%CI -0.02, 0.18), and improved stiffness in OA patients (SMD 0.09; 95%Cl 0.03, 0.20). CONCLUSIONS: Topical NSAIDs are as effective as oral NSAIDs for the treatment of OA and both topical and oral NSAIDs are equally effective in reducing pain and improving physical function in OA patients. In terms of safety, a larger number of samples are still needed to determine if there are any differences in the safety profile of topical or oral NSAIDs. REGISTRATION NUMBER: INPLASY 2021110009.

VSP­17 suppresses the migration and invasion of triple­negative breast cancer cells through inhibition of the EMT process via the PPARγ/AMPK signaling pathway.

VSP­17, a novel peroxisome proliferator­activated receptor γ (PPARγ) agonist, has been previously demonstrated to suppress the metastasis of triple­negative breast cancer (TNBC) by upregulating the expression levels of E­cadherin, which is a key marker of epithelial­mesenchymal transition (EMT). However, the mechanism of action of VSP­17, in particular whether it may be associated with the EMT process, remains unknown. The present study investigated the ability of VSP­17 to inhibit the invasiveness and migratory ability of TNBC cell lines (MDA­MB­231 and MDA­MB­453) performed in in vitro experiments. including cell migration assay, cell invasion assay, cell transfection, RT­qPCR, western blot (WB) analysis and immunofluorescence. The present study aimed to ascertain whether and how the PPARγ/AMP­activated protein kinase (AMPK) signaling pathway serves a role in the inhibitory effects of VSP­17 on cell migration and invasion. The results revealed that both treatment with compound C (an AMPK inhibitor) and transfection with small interfering RNA (si)AMPK notably diminished the inhibitory effect of VSP­17 treatment on the migration and invasion of MDA­MB­231 and MDA­MB­453 cells, indicating that VSP­17 may, at least partly, exert its effects via AMPK. Furthermore, both compound C and siAMPK markedly diminished the VSP­17­induced downregulation of vimentin expression levels and upregulation of E­cadherin expression levels, further indicating that the VSP­17­induced inhibition of the EMT process may be dependent on AMPK. The combination of GW9662 (a PPARγ antagonist) or siPPARγ diminished the inhibitory effect of VSP­17 treatment on the migration and invasion of the TNBC cells, indicating that PPARγ may serve an important role in the VSP­17­induced inhibition of the migration and invasion of TNBC cells. In addition, both GW9662 and siPPARγ significantly reversed the VSP­17­induced downregulation of vimentin expression levels and upregulation of E­cadherin expression levels, implying that the VSP­17­induced inhibition of the EMT process may be dependent on PPARγ. VSP­17 treatment also upregulated the expression levels of p­AMPK, which could be reversed by either GW9662 or siPPARγ, indicating that the VSP­17­induced activation of the AMPK signaling pathway was PPARγ­dependent. In conclusion, the findings of the present study indicated that VSP­17 treatment may inhibit the migration and invasion of TNBC cells by suppressing the EMT process via the PPARγ/AMPK signaling pathway.

Targeting SLC7A11 specifically suppresses the progression of colorectal cancer stem cells via inducing ferroptosis.

Recent studies have revealed the critical roles of ferroptosis in different physiological and pathological processes, however, its effects on the progression of colorectal cancer stem cells (CSCs) are still unclear. Here, we found that colorectal CSCs exhibited a remarkably lower level of reactive oxygen species (ROS), a higher level of cysteine, glutathione and SLC7A11 compared to colorectal cancer cells. Knockout of SLC7A11 increased the ROS level and reduced the levels of cysteine and glutathione, subsequently attenuating the viability of colorectal CSCs. Erastin, an inhibitor of SLC7A11, was found to hold a remarkably stronger cytotoxic effect on colorectal CSCs via in vitro and in vivo experiments. Finally, it was found that Erastin attenuated the chemoresistance of colorectal CSCs. This work indicates that colorectal CSCs are more sensitive to ferroptosis, which could be targeted to attenuate colorectal cancer progression and chemoresistance.

Hepatocyte nuclear factor-1ß suppresses the stemness and migration of colorectal cancer cells through promoting miR-200b activity.

The effects of hepatocyte nuclear factors (HNFs) have been established in various tumors; however, the roles of HNF-1ß in colorectal cancer progression are never been found. In the present study, HNF-1ß expression was initially detected in clinical tissue samples and online datasets and HNF-1ß was found to be highly expressed in colorectal cancer tissues. In addition, a positive correlation existed between HNF-1ß expression and the overall survival of patients with colorectal cancer. In vitro and in vivo experiments revealed that HNF-1ß suppressed the stemness and migration of colorectal cancer cells. Combined with microRNAs (miRNAs) based on transcriptome-sequencing analysis, mechanistic studies showed that HNF-1ß directly bound to miR-200b promoter and thus promoted miR-200b expression, this HNF-1ß/miR-200b resulted in the downregulation of the expression of miR-200b downstream effectors. Furthermore, HNF-1ß inhibits the stemness and migration of colorectal cancer cells through miR-200b. This study reveals a novel HNF-1ß/miR-200b axis responsible for the stemness of colorectal cancer cells.